NK4基因转染对裸鼠人淋巴瘤移植瘤的抑制作用

目的 探讨NK4基因转染对裸鼠人淋巴瘤移植瘤的抑制作用及其机制.方法 采用NK4基因重组质粒pVITRO2-NK4转染的Raji细胞建立裸鼠皮下人淋巴瘤移植瘤模型,动态监测裸鼠体重和肿瘤大小.8周后获取瘤组织,分别采用免疫组化和脱氧核糖核酸末端转移酶介导的缺口末端标记法(TdT-mediated dUTP nick end labeling,TUNEL)检测移植瘤组织的细胞凋亡和微血管密度(microvessel density,MVD),并进行相关分析.结果 NK4基因转染组裸鼠移植瘤体积明显小于对照组(P<0.01),而对照组间差异无显著性(P>0.05);各组间裸鼠体重降低,差异无显著性(P<0.01).NK4基因转染组的淋巴瘤细胞AI值达237±10.94,而质粒pVITRO2转染组和未转染Raji组的AI值分别为79.7±30.8和81.7±22.2,NK4基因转染组明显高于对照组(P<0.001),而对照组间差异无显著性(P>0.05);NK4基因转染组MVD为4.7±1.52,而质粒pVITRO2转染组和未转染Raji组MVD分别为12.0±1.00和10.66±1.53,NK4基因转染组明显低于对照组(P<0.001),而对照组间差异无显著性(P>0.05).结论 NK4基因转染可明显抑制裸鼠人淋巴瘤移植瘤的生长,其可能通过抑制肿瘤血管新生和促肿瘤细胞凋亡而发挥其效应.

Suppression of NK4 gene transfection on human lymphoma xenograft in nude mice

Purpose To study the suppression of NK4 gene transfection on the growth of human lymphoma xenograft in nude mice and its mechanisms.Methods Raji cells transfected by recombinant clone vector pVITRO2-NK4 were used to establish the human lymphoma xenograft in nude mice,then the body weight and tumor size in nude mice were dynamically monitored.After 8 weeks,the tumor tissues were investigated by immunohistochemistry and the terminal deoxynucl neotidyl transferase mediated dUTP nick end labelling(TUNEL) to detect the apoptosis cells and microvessel density(MVD).Result The tumor volume of NK4 gene transfection group was significantly smaller than that in the control groups(P<0.01),while the control groups showed no significant difference(Raji,pVITRO2)(P>0.05).All the groups showed no significant difference in the weight loss of nude mice(P<0.01).The AI of NK4 gene transfection group was 237±10.94,which was significantly lower than that in the control groups(P<0.001).While the plasmid pVITRO2 transfected group and untransfected group were 79.7±30.8 and 81.7±22.2 respectively,the control groups showed no significant difference(Raji,pVITRO2)(P>0.05).The MVD of NK4 gene transfection group was 4.7±1.52,which was significantly lower than that in the control groups(P<0.001),while the plasmid pVITRO2 transfected group and untransfected group were 12.0±1.00 and 10.66±1.53 respectively,the control groups showed no significant difference(Raji,pVITRO2)(P>0.05).Conclusion NK4 gene transfection can significantly inhibit the growth of human lymphoma xenograft in nude mice by promoting the apoptosis and inhibiting the angiogenesis.